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Review
. 2021 Nov 10;22(22):12162.
doi: 10.3390/ijms222212162.

Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases

Manzar Alam  1 , Sabeeha Ali  1 , Sarfraz Ahmed  2 , Abdelbaset Mohamed Elasbali  3 , Mohd Adnan  4 , Asimul Islam  1 , Md Imtaiyaz Hassan  1 , Dharmendra Kumar Yadav  5
Affiliations
Review

Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases

Manzar Alam et al. Int J Mol Sci. .

Abstract

Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.

Keywords: clinical trials; diabetic neuropathy; inflammatory diseases; inhibitors; targeted therapy; ursolic acid.

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Anti-inflammatory and anti-oxidant mechanisms of neuronal function and neuroprotection through UA. Glial cells play a critical function in neuro-inflammation and oxidative stress, common in various neurodegenerative diseases. By repressing the making of ROS, AGEs, and LPO products and enhancing anti-oxidant defenses by upregulation of the Nrf2 signaling, UA shows neuroprotective consequences in neuronal cells (Habtemariam S, 2019). UA has various roles in the CNS. (−), inhibition; (+), promotion; ↓, Decrease; ↑, Increase.
Figure 2
Figure 2
Descriptive proposal of the molecular targets altered through UA in a putative synapse. UA can modulate various receptors, including dopamine D1 and D2. UA might trigger nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) and PI3K/Akt/mTOR, that can inhibit MAPK/NF-κB-mediated pathways. These intracellular pathways’ inflection can provide the expression of proteins involved in cognitive improvement and anti-oxidant and anti-inflammatory effects. D1R, dopamine receptor 1; D2R, dopamine receptor 2; ↓, Decrease; ↑, Increase.
See this image and copyright information in PMC

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